Poor predictive value of broad-range PCR for the detection of arthroplasty infection in 92 cases

Background The diagnosis of prosthetic infection remains a challenge, as no test is 100% sensitive and 100% specific Recent advances in molecular biology have enabled the detection of infection in culture negative cases.

Patients and methods We evaluated the effectiveness of polymerase chain reaction (PCR) in detecting infection in failed joint replacements prospectively in 91 consecutive patients (92 prosthetic joints) undergoing revision total hip or knee arthroplasty. Synovial fluid was collected intraoperatively and examined by broad-range PCR assay for detection of bacterial DNA. The clinical diagnosis of infection was based on the results of blood tests, preoperative joint aspiration, culture and histology of multiple intraoperative tissue samples, as well as the surgeon's assessment.

12 joints (13%) were infected, but the PCR was positive in 32 cases. The sensitivity of the technique was 92%, the specificity 74%, the accuracy 76%, the positive predictive value 34%, and the negative predictive value was 98%.

Interpretation The PCR technique cannot be recommended for the routine detection of prosthetic infection. The large number of false positive results may represent sample contamination, or bacterial presence related to low-virulence organisms, low bacterial load, or a strong host immune response.     

Progression of choroid plexus papilloma

Choroid plexus papillomas are rare neoplasms that arise from choroid plexus epithelium. The World Health Organization classification describes three histological grades. Grade I is choroid plexus papilloma, grade II is atypical choroid plexus papilloma and grade III is choroid plexus carcinoma. Progression between grades is rare but documented. We present two adult cases, a 53-year-old female and a 70-year-old male, who demonstrated clear interval histological progression from grade I choroid plexus papilloma to higher grades.     

Discovery of phthalimide derivatives as novel inhibitors of a soluble epoxide hydrolase

Soluble epoxide hydrolase (sEH) inhibitors are effective in reducing blood pressure, inflammation, and pain in a number of mammalian disease models. As most classical urea-based sEH inhibitors suffer from poor solubility and pharmacokinetic properties, the development of novel sEH inhibitors with an improved pharmacokinetic specification has received a great deal of attention. In this study, a series of amide-based sEH inhibitors bearing a phthalimide ring as the novel secondary pharmacophore (P₂) was designed, synthesized, and evaluated. Docking results illustrated that the amide group as the primary pharmacophore (P₁) was placed at a suitable distance from the three key amino acids (Tyr383, Tyr466, and Asp335) for an effective hydrogen bonding. In agreement with these findings, most of the newly synthesized compounds demonstrated moderate to high sEH inhibitory activities, relative to 12-(3-adamantan-1-yl-ureido)dodecanoic acid as the reference standard. Compound 12e with a 4-methoxybenzoyl substituent exhibited the highest sEH inhibitory activity, with an IC₅₀ value of 1.06 nM. Moreover, the ADME properties of the compounds were evaluated in silico, and the results revealed appropriate predictions.     

Effects of an early referral system on liver transplantation for hepatoblastoma at Texas Children's Hospital

The purposes of this study were to analyze the effects of an ERS on time to transplantation and to describe our center's experience with OLT for HB. Patients who received OLT for HB between 2000 and 2013 were included. Patient and allograft characteristics, chemotherapy regimens, and prior surgical therapies were examined. The interval between diagnosis and OLT prior to and following the institution of an ERS for transplant was compared. Survival and tumor recurrence were analyzed. Nineteen patients received OLT for HB (mean age 33 months). All children received grafts from deceased donors. Two patients underwent prior resections. Tumor recurred in four patients (21.1%). Both patients who received salvage transplants experienced post‐OLT recurrence. Three of the four recurrences occurred in spite of adjuvant chemotherapy. There were three deaths: two from metastatic disease. One‐ and five‐yr survivals were 86.1% and 73.8%. After the institution of the ERS, the mean interval between tissue diagnosis and OLT was significantly reduced. Our series of 19 patients demonstrates a 21% recurrence of HB following OLT despite chemotherapy. Five‐yr survival reached 73.8%. A system of early referral can effectively reduce times between diagnosis and transplant.     

Overview of Dietary Supplements in Prostate Cancer

Prostate cancer is a key health concern for men with its etiology still under investigation. Recently, the role of dietary supplements has been noted to have a major inhibitory effect on prostate cancer and numerous studies have been conducted in this regard. This review provides a summary on numerous recent studies conducted in this field. Some of the studies reviewed revealed a protective role for supplements, and others showed no correlation while some even had an adverse effect. The mechanism of how these supplements act on the prostate is still not clear. Further studies are warranted especially for supplements that have been shown to have a potential inhibitory role in prostate cancer.     

Cytohistomorphological grading of breast carcinoma with special reference to apoptotic rates and lymph node metastasis

To analyze the significance of comparative evaluation of cytohistomorphological grading of infiltrating ductal carcinoma with specific reference to lymphnode metastasis status and apoptotic index. 50 patients who underwent FNAC and mastectomy for infiltrating ductal carcinoma were included in the study. Concordance between cytological and histological grades was calculated. Cytological smears were also evaluated for apoptotic rates and lymph node metastasis and then compared with the histological grades using regression analysis. Histological and cytological grades were comparable and statistically significant difference was found in the lymphnode metastasis rate and apoptotic index in the three cytological grades of the tumor. Moreover, by considering the apoptotic rates, the sensitivity of cytological grading significantly rose in relation to histological grade. With histological grade taken as the standard, cytology was found to be comparable but less sensitive for grading infiltrating ductal carcinoma. However, by considering lymphnode status and apoptotic rates as calculated on cytology, the sensitivity of cytological grading rose significantly in relation to histological grade. Therefore, apoptotic index incorporated with cytological grade may provide relevant information on the aggressiveness of invasive ductal carcinoma of breast and could be a useful parameter to take into consideration when selecting neo-adjuvant therapy.     

<Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> Antigen 85A Induces Th-1 Immune Responses in Systemic Sarcoidosis

Sarcoidosis is a granulomatous disease of unknown etiology, characterized by a Th-1 immunophenotype. Although humoral immune responses by sarcoidosis subjects to mycobacterial proteins have been detected, mycobacterial antigens capable of inducing cellular immune responses in sarcoidosis subjects have not been reported. We used the enzyme-linked immunospot assay to assess for recognition of the Mycobacterium tuberculosis mycolyl transferase, Antigen 85A, by peripheral blood mononuclear cells from 25 sarcoidosis subjects, 22 PPD− (purified protein derivative) healthy volunteers, and 16 PPD+ healthy subjects. Reactivity to Ag85A whole protein was observed in 15 of 25 sarcoidosis subjects compared to 2 of 22 PPD− subjects (p=0.0006, Fisher’s exact test) and to 14 of 16 PPD+ subjects (p=0.084, Fisher’s exact test). Monoclonal antibody against HLA-DR inhibited recognition. In addition to immune recognition of Ag85A whole protein, peptide-mapping studies identified four immunogenic Ag85A peptides, which induced Th-1 immune responses in individual sarcoidosis subjects, suggesting that multiple epitopes from a mycobacterial protein may have a role in sarcoidosis immunopathogenesis.     

Health expenditure,child and maternal mortality nexus: a comparative global analysis

Background

This paper provides empirical evidence on how the relationship between health expenditure and health outcomes varies across countries at different income levels.

Method

Heterogeneity and cross-section dependence were controlled for in the panel data which consist of 161 countries over the period 1995–2014. Infant, under-five and maternal mortality along with life expectancy at birth were selected as health outcome measures. Cross-sectional augmented IPS unit root, panel autoregressive distributed lag, Dumitrescu-Hurlin and Toda-Yamamoto approach to Granger causality tests were used to investigate the relationship across four income groups. An impulse response function modelled the impact on health outcomes of negative shocks to health expenditure.

Results

The results indicate that the health expenditure and health outcome link is stronger for low-income compared to high-income countries. Moreover, rising health expenditure can reduce child mortality but has an insignificant relationship with maternal mortality at all income levels. Lower-income countries are more at risk of adverse impact on health because of negative shocks to health expenditure. Variations in child mortality are better explained by rising health expenditure than maternal mortality. However, the estimated results showed dissimilarity when different assumptions and methods were used.

Conclusion

The influence of health expenditure on health outcome varies significantly across different income levels except for maternal health. Policymakers should recognize that increasing spending has a minute potential to improve maternal health. Lastly, the results vary significantly due to income level, choice of assumptions (homogeneity, cross-section independence) and estimation techniques used. Therefore, findings of the cross-country panel studies should be interpreted with cautions.